The purpose of this research is to expand our knowledge of the genetic elements responsible for the regulation of, and response to, cyclic nucleotide levels in a higher eukaryotic organism. An immediate goal of these studies is to identify genes controlling specific elements in the cyclic nucleotide system: phosphodiesterases, cyclases, calmodulin and cyclic nucleotide binding proteins. The dunce locus in Drosophila melanogaster has been found to control the presence of a cAMP-specific phosphodiesterase activity, to control the level of cAMP in whole flies, to affect learning ability, and to cause sterility in homozygous mutant females. Whether all of these defects are a consequence of the decreased cAMP phosphodiesterase activity of dunce mutants and whether dunce is the structural gene for the enzyme will be investigated. A male-sterile locus just to the left of the dunce locus also affects some aspects of cyclic nucleotide metabolism. This locus will be characterized more extensively both biochemically and genetically and its structural and functional relation to the dunce locus established. Other mutations which also alter cyclic nucleotide phosphodiesterase activities, or otherwise interact with the dunce locus, will be studied to determine the biochemical alterations caused by these mutations.